Contamination of the environment has made toxic metal ions a major health issue. The use of yeasts as model systems for the identification of molecular mechanisms that control sensitivity to these agents is particularly attractive because of the ease of genetic manipulation and the availability of the complete Saccharomyces cerevisiae genomic sequence. This paper reviews information on those genes and mechanisms that have been identified in both the budding yeast S. cerevisiae and the fission yeast Schizosaccharomyces pombe as being capable of modulating sensitivity to important toxic metals. The factors that influence sensitivity to toxic metal ions include cellular thiols (glutathione, phytochelatins, labile sulfide, and metallothioneins) and the products of genes directly and indirectly involved in the transport or sequestration of the metal ion. A complete understanding of the molecular basis of sensitivity to toxic metal ions in lower organisms is expected to provide useful insights in the metal ion detoxification pathways and diseases related to these pathways in humans.